The objective of this proposed research is to elucidate the mechanisms by which certain polyribonucleotides inhibit the growth of cancer cells. We propose to investigate three areas which may illuminate the antitumor mechanism of single and double stranded polynucleotides. First, we wish to study the binding and uptake of exogenous single and double stranded polynucleotides by several cell types derived from normal and cancerous tissues, in order to delineate the biophysical basis of cell-polynucleotide interaction. We have already made initial investigations in this area. Second, we wish to assess direct and selective cytotoxicity of polynucleotides towards tumor cells both in vitro and in vivo. Third, we wish to use the insights gained in the first phases of this study to explore the molecular mechanism whereby double stranded polynucleotides stimulate aggressive behavior in macrophages. We also wish to ascertain if this type of stimulation in manifested by other cells such as lymphocytes; finally, we intend to assess the importance of polynucleotides in antitumor activity in vivo.